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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. January 2008, Volume 7, Number 1, 1-11 |
Computer-Aided Drug Design of Peptide Deformylase (PDF) Inhibitors: A Docking Molecular Modeling Study
Fancui Meng, Weiren Xu, and Xian Zhao
Internet Electron. J. Mol. Des. 2008, 7, 1-11
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Abstract:
Peptide deformylase (PDF) is essential in a variety of pathogenic bacteria but it is
not required for cytoplasmic protein synthesis in eukaryotes, which makes this
enzyme an attractive target for developing novel antibiotics. Because PDF
inhibitors are one of the most promising classes of antibacterial agents discovered
to date, we designed a series of PDF inhibitors and we predicted their biological
activities using molecular simulation methods. Docking simulations of PDF
inhibitors with the ligand binding pocket of PDF have been carried out. The
binding conformations and binding affinities of these inhibitors have been
obtained using the flexible docking protocol FlexX. Calculations performed for
test compounds suggested that FlexX can reproduce the binding conformation of
the crystal structure. Moreover, the predicted binding affinities have a good
correlation with the biological activities of these inhibitors, thus allowing us to
determine the interaction model of PDF inhibitors. A series of designed PDF
inhibitors have been docked to the PDF model and the computed docking scores
have been used as a reference standard to evaluate the activities of these
inhibitors. The results presented in this paper show that several of our designed
compounds are promising PDF inhibitors.
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